Periodontal disease: Does it increase risk of Alzheimer’s disease and mild cognitive impairment?

Participants who reported higher levels of depression and social isolation had greater risk of loneliness, along with people living alone with dementia.

The link between dementia and periodontitis has been a hot topic for the press recently, both in the literature and popular media. Whilst we applaud all attempts to improve the oral hygiene of the population, once claims such as these are advertised, dental professionals are increasingly likely to be questioned by our patients on this worrying new apparent link.  With no cure and its progressive nature, we understand why patients and loved ones strive to comprehend this disease

With 20% of over 65-year-olds suffering from mild cognitive impairment (MCI) in the UK, this is a patient cohort we are very likely to treat. MCI leads to problems with memory or thinking however symptoms are not severe enough to interfere with daily life. Although not a type of dementia, those with mild cognitive impairment are more likely to develop dementia. Alzheimer’s disease (AD) is the most common cause of dementia with 520,000 people in the UK affected. It is caused by abnormal deposits in the brain damaging the nerve cells. This progressively affects memory, language, problem solving and thinking. With our ageing population in mind and a wish to provide the best evidence-based information to our patients, we looked to this systematic review and meta-analysis to clarify if there was a link between exposure to periodontal disease (PD) and AD and MCI.

Method

Searches were conducted in CENTRAL, Medline/Pubmed, Embase, China National Knowledge Internet, China Science and Technology Journal Database, Wanfang Data, www.ClinicalTrials.gov, and WHO International Clinical Trials Registry Platform from inception to September 2020. An adapted combination of medical subject headings (MeSH terms and Emtree terms) and free text linked by Boolean operators were used for electronic searches. Two reviewers independently screened studies according to eligibility criteria and conflicts were adjudicated by a third reviewer. Cohort studies, case-control studies and cross-sectional studies in PD in adults with a diagnosis of AD or MCI were used. The Newcastle-Ottawa scale was used to evaluate the quality of cohort studies and case control studies. Eleven evaluation terms recommended by the Agency for Healthcare Research and Quality (AHRQ) were used to assess the quality of cross-sectional studies. Meta-analysis was conducted for PD and AD and also PD and MCI with a statistical significance set at P < 0.05.

Results

  • 13 studies were included: 5 studies reported on AD, 5 studies reported on MCI and 3 studies reported on both.
  • 8 studies contributed data to the meta-analyses for AD and 8 studies contributed to the meta-analysis for MCI.
  • Different types of studies were included: 5 cross-sectional studies, 5 case-control studies, 2 retrospective cohort studies and a single prospective cohort study.
  • All 3 cohort studies were of high quality along with one case-control study. The remaining studies ranged from medium-high quality.
  • Sensitivity analysis was carried out to ensure the results were robust
  • The results were variable for both AD and MCI
PD and AD PD and MCI
Pooled  results Suggest that periodontal disease is associated with increased risk of developing AD.

OR=1.78, (95%CI; 1.15  to 2.76)

Suggest that periodontal disease is associated with an elevated risk of MCI.

OR=1.60 (95%CI; 1.24 to 2.06)

Subgroup analysis 2 large retrospective cohort studies indicated that that exposure to PD was not related to the risk of AD.

HR 1.29 (95%CI; 0.80-2.06

One prospective cohort study suggests that exposure to PD is related to an increased level of MCI.

OR=2.61 (95%CI; 1.08-6.29

One single cross-sectional study showed no association between PD and AD.

OR= 0.99 (95%CI; 0.37-2.65

This finding was supported by the pooled results of the 4 cross-sectional studies.

OR = 1.5 (95%CI; 1.14-2.02

3 case-control studies showed no association between PD and MC.

OR =2.32 (95%CI; 1.24-4.36

Effect of severity of PD Results suggest that severe PD increased the risk of AD.

OR = 4.89 (95%CI; 1.60-14.97

Results suggest that severe PD increased the risk of MCI.

OR = 2.32 (95%CI; 1.24-4.36

No significant association was found between mild-moderate PD and the risk of AD.

OR = 1.83 (95%CI; 0.93-3.60

No significant association was found between mild-moderate PD and the risk of MCI.

OR = 1.30 (95%CI; 0.94-1.79

  • Most studies adjusted for gender and age when presenting results by using multivariable regression models or matching controls.
  • The cohort studies attempted to adjust for covariates such as co-morbidities, life behaviours, urbanisation, and education level. However, not all studies considered covariates.

Conclusions

The authors concluded:

This study provided a theoretical basis for the prevention of cognitive impairment and AD by early intervention to treat PD. However, the limited number and quality of the included studies indicated that more high-quality cohort and case-control studies are needed to supplement the results.

Comments

A wide search was conducted over multiple databases in an extensive time period, with limited restriction on language. 13 studies were included (5 cross-sectional, 5 case-control, 3 cohort) and risk of bias was reduced by having 2 independent researchers who were adjudicated by a third researcher. Papers were investigated for a link between PD and AD/MCI as appropriate. Results were variable between the pooled data and sub-group analysis data. There was a statistically significant link between severe PD and AD/MCI. The meta-analysis showed there is not a statistically significant link between mild-moderate PD and AD/MCI. There was no continuity in the definitions of PD, AD and MCI between the studies and differing diagnostic criteria were used.  There was a variation in the consideration of co-variates between the different studies which may have had an impact on the results. Three cohort studies were included in the meta-analysis, only one of which was  prospective . Cross-sectional studies may have been less reliable at capturing the progressive nature of periodontal disease, producing misleading results. Overall, we agree that more robust evidence is required to clarify, such as the inclusion of more prospective cohort studies.

Links

Primary paper

Hu Xin, Zhang Jing, Qui Yulan, Lui Zhaonan. Periodontal disease and the risk of Alzheimer’s disease and mild cognitive impairment: a systematic review and meta-analysis. Psychogeriatrics. 2021 Jun. doi: 10.1111/psyg.12743.

Other references

https://nypost.com/2021/04/12/the-disturbing-new-link-between-gum-disease-and-dementia/

 

Authors

This post was written by Carly Ross, Emma O’Donnnel  and Hannah Walthew  Special Care Specialist Trainees based in Scotland following a critical appraisal workshop.

Photo of Carly Photo of Hannah Photo of Emma

 

 

 

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